The natural history of endocrine function and spermatogenesis in Klinefelter syndrome: What the data show

School of Medicine, Boston University, Boston, Massachusetts, USA.
Fertility and sterility (Impact Factor: 4.59). 08/2012; 98(2):266-73. DOI: 10.1016/j.fertnstert.2012.06.024
Source: PubMed


Once thought to be a chromosomal aberration associated with absolute sterility, Klinefelter syndrome may now be potentially treatable by testicular sperm retrieval coupled with intracytoplasmic sperm injection. With these therapeutic advances, azoospermic 47,XXY men now may have an opportunity for biological paternity. However, our knowledge of the basic mechanisms underlying germ cell loss and Leydig cell compromise is lagging, and is just now beginning to evolve and provide answers to some of the field's most vexing questions: how to maximize and preserve fertility in Klinefelter males many years or even decades before they wish to actively pursue fatherhood. This article reviews the development of the androgenic and spermatogenic compartments of the Klinefelter testis through puberty, and recommends that it is only with a clear understanding of the basic facts that a rational, considered approach to fertility optimization and preservation can be determined.

8 Reads
  • Source
    • "The fertilization rate was (statistically) significantly lower in men with KS than in men with non-obstructive azoospermia; however, the pregnancy and abortion rates were found to be similar. These therapeutic advances have provided azoospermic 47, XXY men with an opportunity for biological paternity (Oates, 2012). Despite the success of sperm retrieval and ICSI, many areas of early aggressive hormonal spermatogenesis (and its natural history) and the appropriate management of these patients remains controversial (Mehta and Paduch, 2012;Sigman, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Klinefelter syndrome (KS) is the most common genetic cause of male infertility. Widespread development in assisted reproductive technology has provided non-mosaic KS patients with the opportunity of having biological children. Testosterone replacement therapy and micro-dissection testicular sperm extraction are effective sperm retrieval techniques for KS patients. Despite the success of sperm retrieval and intracytoplasmic sperm injection (ICSI), some areas of early aggressive hormonal spermatogenesis and appropriate management of KS remain controversial. Androgenotherapy, a common treatment for KS, carries a risk of decreasing focal spermatogenesis by lowering the gonadotropin content. Inadequately treated hypogonadism increases psychosocial morbidity in KS patients. Preventive care must be provided from the time of diagnosis, preferentially through a multidisciplinary approach. This indicates the need for improved genetic counseling of KS patients. The aim of this study was to report the prevalence of non-mosaic KS in a Chinese infertile male population. The rate of early diagnosis was lower in KS patients; most of these were diagnosed after rising concerns of reproductive capacity. The mean age of patients with sperm or germ cells was significantly lower, while the semen volume of these patients was significantly higher. However, the semen volume was negatively correlated with the age and ratio of luteinizing hormone/testosterone content in KS patients. Therefore, genetic counseling of KS patients should focus on early diagnosis and timely treatment, in addition to improving the quality of life of all KS patients. The use of testosterone replacement therapy and/ or micro-dissection testicular sperm extraction should be preferentially considered for fertility preservation.
    Preview · Article · Sep 2015 · Genetics and molecular research: GMR
  • [Show abstract] [Hide abstract]
    ABSTRACT: Klinefelter syndrome is commonly encountered by the physician dealing with male infertility. Despite the success of sperm retrieval and ICSI, there remain many areas of controversy about the mechanisms and natural history of spermatogenesis, as well as the appropriate management of these patients. This collection of articles provides a state of the art review of what is known and what is unknown about this syndrome and reports a variety of managment approaches to these patients. (Fertil Steril (R) 2012;98:251-2. (C) 2012 by American Society for Reproductive Medicine.)
    No preview · Article · Jun 2012 · Fertility and sterility
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 47, XXY or Klinefelter syndrome (KS), the most common chromosomal aberration in males, is characterized by either absolute or relative hypogonadism with frequent decline in serum testosterone (T) following the onset of puberty. Decreased T levels are the result of testicular dysfunction with decrease in size of Leydig cells, and loss of germs and Sertoli cells leading to tubular hyalinization. Increase in estradiol results from over-expression of aromatase CYP19. Deficient androgen production and observed varied response of end-organs to T leads to delayed progression of puberty with decreased facial/body hair, poor muscle development, osteoporosis, and gynecomastia. It is possible that hypogonadism and excessive estradiol production contribute to emotional and social immaturity, and specific learning disabilities in KS. Based on the authors' experience and literature review, early fertility preservation and hormonal supplementation may normalize pubertal development, prevent metabolic sequelae of hypogonadism, and have a positive effect on academic and social development. No randomized clinical trials are available studying the effects of T supplementation on reproductive or cognitive issues in KS. Aggressive T supplementation (topical gel) and selective use of aromatase inhibitors may be considered at the onset of puberty with careful follow-up and titration to reach age-specific high-normal physiologic serum values. The decision to institute hormonal therapy should be part of a multidisciplinary approach including physical, speech, behavioral, and occupational therapy. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Feb 2013 · American Journal of Medical Genetics Part C Seminars in Medical Genetics
Show more